For purposes of the present disclosure, “implants” are understood to refer to all nonviable animal or human (xenogeneic or allogeneic) elements or artificial elements which can be introduced into a human or animal body or organism and which remain in the respective organism for at least a certain period of time. Such implants include, for example, stents, pacemakers, artificial heart valves, bone or skin replacement items and depot implants or reservoir implants which serve to release medications over a longer period of time, e.g., depot implants for treatment of cancer such as prostate cancer and biodegradable gentamicin depot implants. These implants consist of a basic body or carrier and optionally additional components. Such an additional component -often includes active pharmaceutical substances such as medicines in or on the body which are released in the body over a certain period of time.
For purposes of the present disclosure, an “active pharmaceutical substance” (or therapeutically active or effective substance) is a vegetable, animal or synthetic active ingredient (medication) or a hormone that is used in a suitable dosage as a therapeutic agent to influence states or functions of the body, as a substitute for active ingredients such as insulin which are naturally produced by the human or animal body, and for eliminating pathogens, tumors, cancer cells or exogenous substances that are rendered harmless. The release of the substance in the environment of the endoprosthesis has a positive effect on the course of healing or serves to render malignant cells harmless in oncology and/or counteracts pathological changes in tissue due to a surgical procedure.
Such active pharmaceutical substances have an anti-inflammatory, anti-proliferative and/or spasmolytic effect, which makes it possible to prevent restenoses, inflammations or (vascular) spasms, for example. In especially preferred exemplary embodiments, such substances may consist of one or more substances from the group of active ingredients consisting of calcium channel blockers, lipid regulators (such as fibrates), immunosuppressants, calcineurin inhibitors (such as tacroliumus), antiphlogistics (such as cortisone or diclofenac), anti-inflammatories (such as imidazoles), anti-allergics, oligonucleotides (such as dODN), estrogens (such as genistein), endothelium-forming agents (such as fibrin), steroids, proteins, hormones, insulins, cytostatics, peptides, vasodilators (such as sartanes) and antiproliferative substances.
Today there is often the desire for these implants that are introduced into the human or animal body to release the active pharmaceutical substances as needed at certain points in time and/or over a certain desired period of time, e.g., depending on the value of a certain bodily function, the blood pressure, and/or in a certain amount in the body, for example, into the surrounding tissue or the surrounding body fluid such as blood. It should be possible for the substance to be dispensed in a process that is controlled by the physician or patient by means of an external device or for the substance to be released automatically, e.g., depending on the values measured by a sensor system for bodily functions. By releasing the active pharmaceutical substance in this way, it is possible to avoid adverse effects for the patient because the active pharmaceutical substance is dispensed only in a desired time window. Therefore, there cannot be any underdosing or overdosing due to such a release.
Treatment of patients by means of stents is an area of applications of particular interest. Stents are endovascular prostheses which can be used for treatment of stenoses (vascular occlusions). They have a tubular or hollow cylindrical basic mesh as a body, preferably comprised of webs as supporting elements folded in a zigzag or meandering pattern and running essentially in the circumferential direction as well as webs as connecting struts running in the longitudinal direction and connecting these supporting elements. The basic mesh is open at both ends in the direction of the axis of the hollow cylinder. The tubular basic mesh of such an endoprosthesis is inserted into the blood vessel that is to be treated and serves to support the vessel. Such stents have become established, in particular, for treatment of vascular diseases. Due to the use of stents, constricted areas in the vessels can be widened, resulting in a larger lumen. After insertion of a stent, there is the risk of a restenosis, i.e., reocclusion of the vascular area treated with the stent because of various processes, for example, coagulation of the body fluid in this area due to a change in blood flow or due to an infectious process. To prevent restenoses, such stents are often provided with active pharmaceutical substances which have an anticoagulant effect, for example. With regard to such a stent, it is also desirable for the active pharmaceutical substances to be released in a controlled manner.
Known stents with medication dispensed from a coating may be made of a polymer, for example. Furthermore, depots of medicine with pumps are also already being used. However, one disadvantage of the known approaches is that the active pharmaceutical substances are released continuously and there is no possibility for regulating the release. Furthermore, only a uniform dosage of the substance is implementable and the amount of medicine remaining in the reservoir or depot cannot be determined. The body of the person or animal being treated is burdened by the continuous release of active ingredients.
International Patent Publication No. WO 2004/093643 discloses an implantable device with which a therapeutic substance is delivered by means of a magnetizable implant to a site that is to be treated. To this end, an implant which is implemented as a stent, for example, has a variety of magnetizable properties, i.e., the property of being permanently magnetic. Because of the magnetizable properties of the implant, the therapeutic substance is attracted so the therapeutic substance is arranged in a magnetic carrier. The magnetic carrier is delivered toward the device by the use of a long-range magnetic field. The known approach thus serves to deliver a therapeutic substance that is administered subsequently to a certain predetermined location in the body. The problem of controlling the release of an active pharmaceutical substance over time is inadequately solved in this way because with the known method, the therapeutic substance is delivered from the site of introduction through the body to the site of the implant. This does not allow an accurate prediction of which point in time and in which amount the desired concentration of the therapeutic substance occurs. Furthermore, the side effects that may result from the delivery of the therapeutic substance through the body are still present as in the past. Furthermore, it is often difficult and time-consuming to arrange the therapeutic substances in a suitable magnetic carrier.
U.S. Pat. No. 7,223,282 discloses an implantable device in the form of a stent which has a first and a second material. The first material has a therapeutic substance. The second material which is carried by the stent serves to convert a first type of energy into thermal energy by means of which the therapeutic substance is released from the first material. However, the thermal energy thereby released cannot be controlled accurately, especially with regard to the quantity released, and under some circumstances, e.g., when excessively high temperatures are reached, the thermal energy can damage the tissue of the patient being treated that surrounds the implantable device.